Summary Heart failure post-myocardial infarction (MI) continues to be the leading cause of death in the U.S. Each year it is estimated that ~550K Americans will have a new MI, and ~200K will have a recurrent MI and a majority of these patients will suffer from heart failure. These staggering statistics necessitate the development of new therapies for patients with ischemic cardiomyopathy. Tissue engineering and regenerative medicine strategies offer significant potential for the development of novel therapies to treat these patients. Recently, acellular biomaterials have shown great promise in providing functional benefit without the complications associated with other regenerative medicine approaches. Injectable biomaterials that stimulate endogenous repair are an attractive alternative since potential therapies could still be delivered minimally invasively via catheter yet could be off the shelf and have significantly reduced costs compared to other regenerative medicine products, such as cells. Ventrix is therefore focusing on cell-free regenerative medicine approaches. Ventrix has a history of success in developing injectable biomaterials for treating ischemic cardiomyopathy. Two previous NIH SBIRs resulted in an approved IND for VentriGel, an injectable, catheter-deliverable hydrogel derived from decellularized porcine myocardium. This led to a recent successful Phase 1 clinical trial in patients 60 days to 3 years post-MI. The study proposed herein is a key step in bringing a new biomaterial product to market for treating acute MI. This new soluble version of VentriGel can be delivered via intracoronary infusion, which will enable treatment immediately post-MI, unlike the original formulation, which required transendocardial delivery. Herein, we will test the feasibility of translating this new technology by optimizing delivery and evaluating function in a large animal acute MI model. This will be the first intracoronary infusible regenerative biomaterial product for treating acute MI patients.